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We have studied whether the Warburg effect (uncontrolled glycolysis) in pancreatobiliary adenocarcinoma triggers cachexia in the patient. After 74 pancreatobiliary adenocarcinomas were removed by surgery, their glucose transporter-1 and four glycolytic enzymes were quantified using Western blotting. Based on the resulting data, the adenocarcinomas were equally divided into a group of low glycolysis (LG) and a group of high glycolysis (HG). Energy homeostasis was assessed in these cancer patients and in 74 non-cancer controls, using serum albumin and C-reactive protein and morphometrical analysis of abdominal skeletal muscle and fat on computed tomography scans. Some removed adenocarcinomas were transplanted in nude mice to see their impacts on host energy homeostasis. Separately, nude mice carrying tumor grafts of MiaPaCa-2 pancreatic adenocarcinoma cells were treated with the glycolytic inhibitor 3-bromopyruvate and with emodin that inhibited glycolysis by decreasing hypoxia-inducible factor-1α. Adenocarcinomas in both group LG and group HG impaired energy homeostasis in the cancer patients, compared to the non-cancer reference. The impaired energy homeostasis induced by the adenocarcinomas in group HG was more pronounced than that by the adenocarcinomas in group LG. When original adenocarcinomas were grown in nude mice, their glycolytic abilities determined the levels of hepatic gluconeogenesis, skeletal muscle proteolysis, adipose-tissue lipolysis, and weight loss in the mice. When MiaPaCa-2 cells were grown as tumors in nude mice, 3-bromopyruvate and emodin decreased tumor-induced glycolysis and cachexia, with the best effects being seen when the drugs were administered in combination. In conclusion, the Warburg effect in pancreatobiliary adenocarcinoma triggers cancer cachexia.
Assuntos
Adenocarcinoma , Emodina , Neoplasias Pancreáticas , Camundongos , Animais , Adenocarcinoma/patologia , Caquexia/etiologia , Caquexia/metabolismo , Neoplasias Pancreáticas/patologia , Camundongos NusRESUMO
BACKGROUND: There is currently no standardized treatment for Mirizzi's syndrome (MS). We aim to explore the surgical treatment strategy for MS by analyzing its clinical characteristics and treatment outcomes. METHODS: This retrospective study analyzed the clinical data of 130 patients with MS who underwent surgery at our hospital from April 2013 to April 2020. RESULTS: The study population comprised 130 patients with MS, with an approximately balanced sex ratio and a median age of 58.5 years. The preoperative diagnostic rate was 82.3%. The diagnostic accuracy of ERCP was 92.5%, higher than that of MRCP and ultrasound. All patients underwent surgical treatment, with 74 cases of laparoscopic surgery, 43 cases of laparotomy, and 13 cases of laparoscopic surgery converted to laparotomy. A total of 23 patients experienced short-term and long-term complications after surgery, with a complication rate of 17.7%. There was no statistical difference between laparoscopic surgery and open surgery in terms of intraoperative hemorrhage, operative time, and postoperative complication rate. However, the length of hospital stay was shorter in the laparoscopic surgery compared to the open surgery, which was statistically different from each other. CONCLUSION: ERCP is the gold standard for the diagnosis of MS, especially for identifying the type of MS. ERCP plays an important role in both the preoperative and postoperative phases of MS. Our study demonstrated that laparoscopic surgery was a safe and feasible option for MS treatment, even requires less hospitalization than open surgery.
RESUMO
Aim: To evaluate the anti-pancreatic cancer effect of novel Tubeimoside I multifunctional liposomes combined with gemcitabine.Methods: Liposomes were prepared through the thin film hydration method, with evaluations conducted on parameters including encapsulation efficiency (EE%), particle size, polydispersity index (PDI), zeta potential (ZP), storage stability, and release over a 7-day period. The cellular uptake rate, therapeutic efficacy in vitro and in vivo and the role of immune microenvironment modulation were evaluated.Results: The novel Tubeimoside I multifunctional liposomal exhibited good stability, significant anti-cancer activity, and immune microenvironment remodeling effects. Furthermore, it showed a safety profile.Conclusion: This study underscores the potential of Novel Tubeimoside I multifunctional liposomal as a promising treatment option for pancreatic cancer.
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